Standard Versus Extended Lymphadenectomy in Pancreatoduodenectomy for Patients With Pancreatic Head Adenocarcinoma

NCT ID: NCT02928081

Last Updated: 2016-10-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 320 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2021-04-30

Brief Summary

The aim of this study is to determine whether the performance of extended lymphadenectomy in association with pancreatoduodenectomy improves the long-term survival in patients with pancreatic head ductal adenocarcinoma.Half of participants will receive pancreatoduodenectomy with extended lymphadenectomy,while the other half will receive pancreatoduodenectomy with standard lymphadenectomy.

Detailed Description

Pancreatic cancer is a common malignant disease of the digestive system, and its incidence has been steadily increasing recently. Currently, the only potential curative treatment for pancreatic cancer is radical surgery. However, due to the peculiarity of the anatomical location of pancreas (in the retroperitoneum, surrounded by peripheral nerves and blood vessels) and its biological characteristics (neurotropic, highly malignant, and with probable skip metastasis), it is difficult to achieve R0 resection in patients with pancreatic cancer. High postoperative recurrence and distant metastasis rate are key factors in reducing long-term survival of patients with pancreatic cancer. The radical surgery modalities for pancreatoduodenectomy to achieve R0 resection involve extended lymphadenectomy, multivisceral resections, with or without simultaneous vein removals. Currently, the lymphadenectomy extent and approaches used to achieve R0 status are diverse. In 2014, the International Study Group for Pancreatic Surgery (ISGPS) reached a consensus to strive to resect lymph nodes (LNs) 5, 6, 8a, 12b1, 12b2, 12c, 13a, 13b, 14a, 14b, 17a, and 17b in standard lymphadenectomy for pancreatoduodenectomy. However, no consensus was reached on dissection of LN 16 due to variation in the literature and different expert opinions. On the current evidence, benefit of extended lymph node dissection seems to be outweighed by the risks. But deficiencies exist in the design of previous RCTs, such as insufficient sample size, lack of certain critical data for statistical analysis, inclusion of other pathological types of pancreatic neoplasms and variable retroperitoneal lymph node resection and nerve plexus dissection . Therefore, the power of evidence was low. Most studies report a high frequency of lymph node metastasis to LNs 13, 14, 17, 12 and 16 in pancreatic cancer, and tendency to metastasis from LNs 13, 14 to LN 16. In a lot of case reports, only nodal station 16a2 and 16b1 were positive in LN 16.

This study is performed to confirm whether pancreatoduodenectomy with extended lymphadenectomy could improve survival. Subjects undergoing surgery will be randomized to pancreatoduodenectomy with extended lymphadenectomy including nerve tissues around CHA and the SMA and nodes around the celiac trunk and SMA (No.16a2, 16b1) versus standard pancreatoduodenectomy. Subjects will be followed every three months for survivorship or death. The primary endpoint of 5-year overall or disease-free survival survival will be determined at five year post surgery.

Conditions

Carcinoma, Pancreatic Ductal

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Extended lymphadenectomy

In addition to the standard lymphadenectomy, the nerve tissues around CHA and the SMA and nodes around the celiac trunk and SMA (No.16a2, 16b1) must be dissected. Retroperitoneal lymphatic tissue, nerves and connective tissue range from the hepatic portal down to the beginning part of the inferior mesenteric artery, the right to the right renal hilus, left to the left edge of the abdominal aorta is included.

Group Type: EXPERIMENTAL

Extended lymphadenectomy

Intervention Type: PROCEDURE

Extended lymphadenectomy with nerve tissues around CHA and the SMA and nodes around the celiac trunk and SMA (No.16a2, 16b1)

Standard lymphadenectomy

Lymph node dissection includes the superior and inferior pyloric nodes (LN5, LN6), anterior and posterior nodes along the common hepatic artery (CHA) (LN8a, 8b), nodes along the common hepatic duct, common bile duct and cystic duct (LN12b1, 12b2, 12c), posterior pancreatoduodenal nodes (LN13a, 13b), nodes along the superior mesenteric artery (SMA) (LN14a, 14b), anterior pancreatoduodenal nodes (LN17a, 17b), but excluding the nerve tissues around common hepatic artery and the superior mesenteric artery.

Group Type: OTHER

Standard lymphadenectomy

Intervention Type: PROCEDURE

Lymph node dissection includes(LN5, LN6),(LN8a, 8b),(LN12b1, 12b2, 12c),(LN13a, 13b),(LN14a, 14b),(LN17a, 17b)

Interventions

Extended lymphadenectomy

Extended lymphadenectomy with nerve tissues around CHA and the SMA and nodes around the celiac trunk and SMA (No.16a2, 16b1)

Intervention Type: PROCEDURE

Standard lymphadenectomy

Lymph node dissection includes(LN5, LN6),(LN8a, 8b),(LN12b1, 12b2, 12c),(LN13a, 13b),(LN14a, 14b),(LN17a, 17b)

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Subject was diagnosed with pancreatic ductal adenocarcinoma supported by pathological and radiological examination preoperatively
• Subject with absence of vascular invasion and metastasis
• Subject with absence of prior history of cancer

Exclusion Criteria

• Subject was diagnosed that other pancreatic tumour types (neuroendocrine tumors, intraductal papillary mucinous neoplasm, serous cystadenoma, mucinous cystadenocarcinoma, solid pseudopapillary neoplasm and pancreatitis)
• Subject was found with liver, omental, mesenteric or peritoneal metastasis intraoperatively
• Subject with presence of other significant diseases (e.g., coronary heart disease)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Royal Liverpool University Hospital

OTHER_GOV

Sponsor Role: collaborator

West China Hospital

OTHER

Sponsor Role: lead

Responsible Party

Chen Hongyu

Hongyu Chen,MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hongyu Chen, MD

Role: PRINCIPAL_INVESTIGATOR

West China Hospital

Locations

West China Hospital

Chengdu, Sichuan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xubao Liu, MD

Role: CONTACT

liuxb2011@126.com

86-28-85422474

Junjie Xiong, MD

Role: CONTACT

junjiex2011@126.com

86-28-85422474

Facility Contacts

Xubao Liu, MD

Role: primary

liuxb2011@126.com

86-28-85422474

Junjie Xiong, MD

Role: backup

junjiex2011@126.com

86-28-85422474

References

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Reference Type: BACKGROUND

PMID: 27149448 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 25042895 (View on PubMed)

Chen Y, Ke N, Tan C, Zhang H, Wang X, Mai G, Liu X. Continuous versus interrupted suture techniques of pancreaticojejunostomy after pancreaticoduodenectomy. J Surg Res. 2015 Feb;193(2):590-7. doi: 10.1016/j.jss.2014.07.066. Epub 2014 Aug 5.

Reference Type: RESULT

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Chen Y, Tan C, Mai G, Ke N, Liu X. Resection of pancreatic tumors involving the anterior surface of the superior mesenteric/portal veins axis: an alternative procedure to pancreaticoduodenectomy with vein resection. J Am Coll Surg. 2013 Oct;217(4):e21-8. doi: 10.1016/j.jamcollsurg.2013.07.383. No abstract available.

Reference Type: RESULT

PMID: 24054418 (View on PubMed)

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Reference Type: RESULT

PMID: 25141915 (View on PubMed)

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Reference Type: RESULT

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Jang JY, Kang MJ, Heo JS, Choi SH, Choi DW, Park SJ, Han SS, Yoon DS, Yu HC, Kang KJ, Kim SG, Kim SW. A prospective randomized controlled study comparing outcomes of standard resection and extended resection, including dissection of the nerve plexus and various lymph nodes, in patients with pancreatic head cancer. Ann Surg. 2014 Apr;259(4):656-64. doi: 10.1097/SLA.0000000000000384.

Reference Type: RESULT

PMID: 24368638 (View on PubMed)

Wang Z, Ke N, Wang X, Wang X, Chen Y, Chen H, Liu J, He D, Tian B, Li A, Hu W, Li K, Liu X. Optimal extent of lymphadenectomy for radical surgery of pancreatic head adenocarcinoma: 2-year survival rate results of single-center, prospective, randomized controlled study. Medicine (Baltimore). 2021 Sep 3;100(35):e26918. doi: 10.1097/MD.0000000000026918.

Reference Type: DERIVED

PMID: 34477122 (View on PubMed)

Other Identifiers

2015267

Identifier Type: -

Identifier Source: org_study_id